MicroRNA 375 modulates hyperglycemia-induced enteric glial cell apoptosis and Diabetes-induced gastrointestinal dysfunction by targeting Pdk1 and repressing PI3K/Akt pathway.
MicroRNA 375 modulates hyperglycemia-induced enteric glial cell apoptosis and Diabetes-induced gastrointestinal dysfunction by targeting Pdk1 and repressing PI3K/Akt pathway.
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MicroRNA 375 通过靶向 Pdk1 和抑制 PI3K/Akt 通路调节高血糖诱导的肠胶质细胞凋亡和糖尿病诱导的胃肠功能障碍
DOI：
10.1038/s41598-018-30714-0
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发表时间：
2018-08-23
影响因子：
4.6
通讯作者：
Gan H
中科院分区：
文献类型：
--
作者：
Chen Y;Liu G;He F;Zhang L;Yang K;Yu H;Zhou J;Gan H
糖尿病神经病变可引起全身神经系统损害，包括肠神经系统改变和胃肠道功能障碍。糖尿病对肠胶质细胞（EGC）的影响尚不清楚。我们研究了糖尿病和高血糖对EGC的影响，以及microRNA 375在体内和体外调节EGC存活中的作用。链脲佐菌素诱导的糖尿病小鼠腹腔注射microRNA 375抑制剂或其阴性对照。用microRNA 375抑制剂或其模拟物转染EGC。伴有胃肠功能障碍的糖尿病小鼠显示EGC凋亡增加（细胞数量无差异）和肌间神经丛中micorRNA 375的基因表达增加。高脂血症诱导EGC凋亡，Pdk 1和p-Akt表达降低，micorRNA 375表达增加。MicorRNA 375模拟物通过抑制Pdk 1和p-Akt诱导EGC凋亡MicorRNA 375抑制剂在体外可预防高血糖诱导的EGC凋亡，在体内可预防糖尿病诱导的胃肠功能障碍。我们的研究结果表明，糖尿病引起的胃肠功能障碍与肌间神经丛EGC凋亡增加有关。高血压可通过PI 3 K/Akt通路增加microRNA 375的表达，损害EGC的存活。MicroRNA 375特异性抑制可预防高血糖引起的EGC损伤和糖尿病引起的胃肠功能障碍。
Diabetic neuropathy can damage systemic nervous system, including alteration of enteric nervous system and subsequent gastrointestinal dysfunction. The effect of diabetes on enteric glia cell (EGC) is not clear. We investigated the effect of diabetes and hyperglycemia on EGC, and the role of microRNA375 in modulating EGC survival in vivo and in vitro. Streptozotocin-induced diabetic mice were intraperitoneally injected with microRNA375 inhibitor or its negative control. EGC was transfected with microRNA375 inhibitor or its mimic. Diabetes mice with gastrointestinal dysfunction showed increased apoptosis of EGC (no difference in cell numbers) and gene expression of micorRNA375 in the myenteric plexus. Hyperglycemia triggered apoptosis of EGC in vitro with decreased expression of Pdk1 and p-Akt, but increased expression of micorRNA375. MicorRNA375 mimic induced apoptosis of EGC in vitro with repressed Pdk1and p-Akt. MicorRNA375 inhibitor could both prevent hyperglycemia-induced apoptosis of EGC in vitro and diabetes-induced gastrointestinal dysfunction in vivo. Our results suggest that diabetes-induced gastrointestinal dysfunction is related to increased apoptosis of EGC in the myenteric plexus. Hyperglycemia can increase the expression of microRNA375 and damage EGC survival through PI3K/Akt pathway. MicroRNA375 specific inhibition can prevent hyperglycemia induced EGC damage and diabetes-induced gastrointestinal dysfunction.
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DOI：
10.1007/s11938-017-0151-1
发表时间：
2017-12
期刊：
Current treatment options in gastroenterology
影响因子：
--
作者：
Piper MS;Saad RJ
通讯作者：
Saad RJ
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
1.4
作者：
Furlan, Maria Montserrat D.P.;Molinari, Sônia L.;Miranda Neto, Marcílio H. de
通讯作者：
Miranda Neto, Marcílio H. de
影响因子：
5.5
作者：
Baudry, Charlotte;Reichardt, Francois;Moriez, Raphael
通讯作者：
Moriez, Raphael
影响因子：
24.5
作者：
Bassotti, G;Villanacci, V;Salemi, B
通讯作者：
Salemi, B